TIGER – Advancing Exploratory Biomarkers
Current post-cancer monitoring relies on patient-reported symptoms followed by physical examination, imaging methods, and blood tests. However, there are inherent limitations of traditional imaging and physical examination while conventional blood tests are not sensitive enough for routine cancer monitoring.
Imaging
Imaging is the main tool used by physicians to see if a previously treated cancer has returned, or is spreading to other locations, but due to the issue of false-positives and false-negatives, it is typically only used when there is a suspicion of relapse based on reported symptoms and/or physical exam. Although imaging is a valuable tool and can be used for disease location, imaging can only detect tumours once they have become relatively large, meaning catching the disease at its most treatable state can be missed. Imaging can be prone to overdiagnosis leading to unnecessary patient stress and overtreatment. Radiomics will address these shortcomings from an imaging perspective in the TIGER project.
ctDNA
Tissue biopsies are known for their invasiveness, impracticality, and high costs (not to mention the difficulties in identifying resistance mechanisms and potential needs to repeat biopsy). Tumours can be missed, and multiple tumours can rarely be biopsied at the same time, while invasive biopsies can lead to significant (and costly) complications. The shortcomings of existing blood-based biomarkers consist of protein biomarkers that too frequently give false positives and false-negatives and do not provide information about targetable mutations or tumour heterogeneity.
The availability of accurate tests to guide treatment, monitor therapy, and detect recurrence from simple blood draws would revolutionise cancer care. However, progress in this direction has been hampered by the lack of reliable tumour-specific biomarkers used in current tests. A promising alternative lies in recovering and analysing tumour-shed materials circulating in the patient’s body. In fact, the presence of circulating tumour DNA (ctDNA) in cancer patients has been known for decades. But, until recently, distinguishing the low levels of ctDNA from the total normal cell-free DNA shed by all cells (cancerous or otherwise) has proved challenging. SAGA Diagnostics will address this challenge in the TIGER project.
Immune monitoring
Immune monitoring is used to assess a patient’s immune response during treatment to see whether immune cells are functional or non-functional, and gain understanding if a treatment is working. Understanding how a cancer treatment impacts a patient’s immune response is important for improving cancer therapies. To perform immune monitoring, blood or tumor tissue samples are used to test and define properties in the patient’s cells that correspond with successful or unsuccessful therapy. VUMC-CCA Immunotherapy Lab will undertake this work in the TIGER project.